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Tuning Structures and Properties for Developing Novel Chemical Tools toward Distinct Pathogenic Elements in Alzheimer's Disease

Tuning Structures and Properties for Developing Novel Chemical Tools toward Distinct Pathogenic Elements in Alzheimer's Disease
Han, JiyeonLee, Hyuck JinKim, Kyu YeonLee, Shin Jung C.Suh, Jong-MinCho, Jae HeungChae, JunghyunLim, Mi Hee
DGIST Authors
Cho, Jae Heung
Issue Date
ACS Chemical Neuroscience, 9(4), 800-808
Article Type
Alzheimer&aposs diseasechemical toolsredox propertiesmetal-freeamyloid-betametal-bound amyloid-betafree radicalsamyloid-beta-peptidemetal-catalyzed oxidationa-betaantioxidantcapacitysmall moleculescyclic voltammetryaggregationneurotoxicityinhibitorsdesign
Multiple pathogenic factors [e.g., amyloid-β (Aβ), metal ions, metal-bound Aβ (metal-Aβ), reactive oxygen species (ROS)] are found in the brain of patients with Alzheimer's disease (AD). In order to elucidate the roles of pathological elements in AD, chemical tools able to regulate their activities would be valuable. Due to the complicated link among multiple pathological factors, however, it has been challenging to invent such chemical tools. Herein, we report novel small molecules as chemical tools toward modulation of single or multiple target(s), designed via a rational structure-property-directed strategy. The chemical properties (e.g., oxidation potentials) of our molecules and their coverage of reactivities toward the pathological targets were successfully differentiated through a minor structural variation [i.e., replacement of one nitrogen (N) or sulfur (S) donor atom in the framework]. Among our compounds (1-3), 1 with the lowest oxidation potential is able to noticeably modify the aggregation of both metal-free Aβ and metal-Aβ, as well as scavenge free radicals. Compound 2 with the moderate oxidation potential significantly alters the aggregation of Cu(II)-Aβ42. The hardly oxidizable compound, 3, relative to 1 and 2, indicates no noticeable interactions with all pathogenic factors, including metal-free Aβ, metal-Aβ, and free radicals. Overall, our studies demonstrate that the design of small molecules as chemical tools able to control distinct pathological components could be achieved via fine-tuning of structures and properties. © 2017 American Chemical Society.
American Chemical Society
Related Researcher
  • Author Cho, Jaeheung Biomimetic Materials Laboratory
  • Research Interests Biomimetics; Metalloenzymes; Nitric Oxide Suppliers in Brain; Biomimetic Materials in Life
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Department of Emerging Materials ScienceBiomimetic Materials Laboratory1. Journal Articles

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